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The BLAST- 1 Trial - Cephalexin+Amoxicillin-clavulanate for Tuberculosis
The goal of this randomized controlled trial is to study the early bactericidal activity in adult patients with smear-positive pulmonary tuberculosis. The main question it aims to answer are if cephalexin, in combination with amoxicillin-clavulanate, is effective in the treatment of tuberculosis. Participants with smear-positive tuberculosis will be randomized to either of two groups: Intervention group: cephalexin and amoxicillin-clavulanate.
Control group: Standard of care TB treatment. The study period is 2 weeks and participants will be asked to submit multiple sputum samples to measure the bacterial sputum load. They will also submit saliva samples for estimation of drug concentrations in the body.
Researchers will compare the intervention group with the control group to see if the trial drugs result in a reduced bacterial sputum load Overall aim: To study the early bactericidal activity of cephalexin, in combination with amoxicillin-clavulanate, in comparison to standard treatment in patients with active pulmonary tuberculosis during the first 2 weeks of treatment. Primary aim: 1. To evaluate the early bactericidal activity (measured as 'time to culture positivity') of cephalexin-clavulanate in comparison, to standard TB treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol).
Secondary aim: 2. To asses safety and tolerability of cephalexin together with amoxicillin-clavulanate. 3.
To determine key pharmacokinetic (PK) parameters of cephalexin, especially half-life and drug exposure (maximal concentration; Cmax and area under the concentration versus time curve, AUC).
Study details:
Given the need for alternative and well-tolerated tuberculosis (TB) treatment options, there is scope to re-assess the potential value of already approved drugs that are known to be safe, cheap and widely available. Cephalexin, in combination with amoxicillin-clavulanate, have shown high in vitro efficacy against the TB bacteria. Both cephalexin and amoxicillin-clavulanate are Therapeutic Goods Administration (TGA) approved and are widely used in Australia for common infections.
In order to compare the bacterial killing effect of cephalexin, in combination with amoxicillin-clavulanate, with current standard of care TB treatment, we will perform an open-label randomized controlled trial. Eligible and consenting study participants with bacteriologically confirmed sputum-smear positive pulmonary TB will be randomised to an intervention or control arm in a 1:1 ratio (15 patients in each arm) for the two weeks duration of the trial. * Intervention arm: cephalexin 1g thrice daily + amoxicillin-clavulanate 500/125 mg thrice daily.
* Control arm: standard of care treatment for TB (rifampicin, isoniazid, ethambutol and pyrazinamide) The primary outcome is the fall in bacterial load measured by 'time to positive culture' using the BACTEC MGIT system with automated detection. Multiple sputum samples (10 in total) will be collected during the first 2 weeks of TB treatment. Six saliva samples will be collected after 4 days of treatment, in order to estimate the drug concentrations of cephalexin in the body (intervention arm only).
For a small subset of patients receiving cephalexin (n=5), a more intensive simultaneous blood and saliva sampling will be done in order to calculate the saliva:plasma ratio, in order to facilitate the estimation of plasma drug concentrations from saliva samples.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-03-15
Primary completion: 2024-07-01
Study completion finish: 2024-12-01
Study type
TREATMENT
Phase
PHASE2
Trial ID
NCT05664568
Intervention or treatment
DRUG: Cephalexin
DRUG: Amoxicillin-Clavulanate 500 Mg-125 Mg Oral Tablet
OTHER: Standard of care treatment of tuberculosis
Conditions
- • Tuberculosis, Pulmonary
Find a site
Closest Location:
Blacktown Hospital
Research sites nearby
Select from list below to view details:
Blacktown Hospital
Sydney, Not Specified, Australia
Royal Prince Alfred Hospital
Sydney, Not Specified, Australia
Western Sydney Health District
Sydney, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ACTIVE_COMPARATOR: Standard of care TB
| OTHER: Standard of care treatment of tuberculosis
|
EXPERIMENTAL: Cephalexin + amoxicillin-clavulanate
| DRUG: Cephalexin
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| Time to positivity (TTP) | Early bactericidal activity measured as fall in time to positivity (TTP) 1. The primary outcome is fall in bacterial load in sputum, measured as the rate of change in Time to Sputum Culture Positivity (TTP). TTP is the time to a positive culture when sputum samples are incubated in BACTEC MGIT for automated detection of M. tuberculosis. Measuring the fall in bacterial load is standard choice of outcome for studies evaluating the effect (kill) of drug on TB bacteria. | 2 weeks |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Adverse events | Tolerability - frequency, categorization and grade of adverse events according to CTCAE (Common Terminology Criteria for Adverse Events) | 2 weeks |
| Area under the concentration versus time curve (AUC) of cephalexin | Estimation of the pharmacokinetic parameter area under the concentration versus time curve (AUC) of cephalexin in saliva. | 2 weeks |
| Cmax of cephalexin | Estimation of the pharmacokinetic parameter maximum concentration (Cmax) of cephalexin saliva. | 2 weeks |
Frequently Asked Questions
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